European patent application No. 0,061,712, published Oct. 6, 1982 discloses compounds of the formula, ##STR2## where Q is pyridyl, thienyl or a group of the formula ##STR3## These compounds are disclosed as possessing antiinflammatory and/or analgesic activity,
U.S. Pat. No. 3,792,057 issued to Jensen on Feb. 12, 1974, discloses compounds of the formula ##STR4## where R.sub.1 may be methylthio as inhibitors of phenylethanolamine-N-methyl transferase and also as fungicides and coccidiostats.
There is a continuing need for safe and effective antiinflammatory agents. Inflammation is a disease process characterized by redness, fever, swelling and pain. Arthritis, in its various forms, is the most prevalent, chronic, and severe of the inflammatory diseases. Traumatic injury and infection also involve inflammation, and antiinflammatory drugs are often used in their treatment. The usefulness of most commercial antiinflammatories is limited, however, because of toxicity and adverse side-effects. Many produce gastric irritation and other effects, such as changes in blood cells and in the central nervous system. Adrenocortical steroids produce gastric irritation and suppression of normal adrenal function.
Dysmenorrhea is a painful condition associated with menstruation which affects an estimated 30-50 percent of women of childbearing age causing the loss of more than 140 million working hours per year [J. L. Marx, Science, 205, 175 (1979)]. The symptoms of dysmenorrhea include nausea, vomiting, diarrhea, and headache. Abnormally high levels of prostaglandin compounds occur in the endometrium and menstrual fluid of patients suffering from primary dysmenorrhea. Prostaglandins are known to cause uterine contractions, sensitize nerve endings to pain. and cause the typical symptoms of the condition. Treatment of dysmenorrhea with prostaglandin synthetase inhibitors reduces prostaglandin levels and relieves the symptoms of dysmenorrhea [M. R. Henzl and A. Izu, Acta. Obstet. Gynecol. Scand. Suppl., 87, 105 (1979) and W. Y. Chan, M. Y. Dawood, and F. Fuchs, Am. J. Obstet. Gynecol., 135, 102 (1979)].
There is thus a clear need for improved antiinflammatory agents, especially ones which also possess activity as prostaglandin synthetase inhibitors which would be independently useful for treatment of primary dysmenorrhea.
The present invention results from efforts to develop new anti-arthritic compounds with good antiinflammatory activity and minimal side effects that could be more effective in treating arthritis than presently available drugs.
In addition to antiinflammatory properties, some compounds of this invention demonstrate analgesic activity in a test procedure. This additional property is desirable in treatment of arthritis or related diseases; however, such compounds can be employed solely to alleviate pain.
In addition, compounds of this invention are inhibitors of prostaglandin synthetase and as such are useful for the treatment of primary dysmenorrhea.